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Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma.

ABSTRACT: S100A16 is a conserved member of the S100 protein family in mammals. Its upregulation was observed in many tumors and is related to malignant transformation. In this study, we explored the independent prognostic value of S100A16 in terms of overall survival (OS) and recurrence-free survival (RFS) by performing a retrospective study, using data in The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD). Besides, by using deep sequencing data in TCGA-LUAD, we also explored the association between S100A16 expression and its DNA methylation and copy number alterations (CNAs). Results showed that the primary LUAD tissues (N = 514) had significantly elevated S100A16 expression compared with the normal lung tissues (N = 59). Based on OS data of 502 primary LUAD cases, we found that high S100A16 expression was correlated with inferior OS. The following univariate and multivariate analysis confirmed that increased S100A16 expression was an independent prognostic indicator of unfavorable OS (HR: 1.197, 95%CI: 1.050-1.364, p = 0.007) and RFS (HR: 1.206, 95%CI: 1.045-1.393, p = 0.011). By examining the DNA methylation data in TCGA-LUAD, we found that some S100A16 DNA CpG sites were generally hypermethylated in normal tissues, but not in LUAD tissues. Regression analysis identified a moderately negative correlation between S100A16 expression and its DNA methylation. In comparison, although DNA amplification (+1/+2) was frequent (378/511, 74%) in LUAD patients, it was not associated with increased S100A16 expression. Based on findings above, we infer that aberrant S100A16 expression might be modulated by its DNA hypomethylation and serves as an independent prognostic indicator of unfavorable OS and RFS in LUAD.

SUBMITTER: Chen

PROVIDER: S-EPMC5945035 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma.

Chen De Luo Linjie L Liang Chao C

PloS one 20180510 5

S100A16 is a conserved member of the S100 protein family in mammals. Its upregulation was observed in many tumors and is related to malignant transformation. In this study, we explored the independent prognostic value of S100A16 in terms of overall survival (OS) and recurrence-free survival (RFS) by performing a retrospective study, using data in The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD). Besides, by using deep sequencing data in TCGA-LUAD, we also explored the association betwee ...[more]

PMID: 29746588

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Project description:BackgroundGlucosamine-Phosphate N-Acetyltransferase 1 (GNPNAT1) is a critical enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine. It has many important functions, such as protein binding, monosaccharide binding, and embryonic development and growth. However, the role of GNPNAT1 in lung adenocarcinoma (LUAD) remains unclear.MethodsIn this study, we explored the expression pattern and prognostic value of GNPNAT1 in LUAD across TCGA and GEO databases and assessed its independent prognostic value via Cox analysis. LinkedOmics and GEPIA2 were applied to investigate coexpression and functional networks associated with GNPNAT1. The TIMER web tool was deployed to assess the correlation between GNPNAT1 and the main six types of tumor-infiltrating immune cells. Besides, the correlations between GNPNAT1 and the LUAD common genetic mutations, TMB, and immune signatures were examined.ResultsGNPNAT1 was validated upregulated in tumor tissues in TCGA-LUAD and GEO cohorts. Moreover, in both TCGA and GEO cohorts, high GNPNAT1 expression was found to be associated with poor overall survival. Cox analysis showed that high GNPNAT1 expression was an independent risk factor for LUAD. Functional network analysis suggested that GNPNAT1 regulates cell cycle, ribosome, proteasome, RNA transport, and spliceosome signaling through pathways involving multiple cancer-related kinases and E2F family. In addition, GNPNAT1 correlated with infiltrating levels of B cells, CD4+ T cells, and dendritic cells. B cells and dendritic cells could predict the outcome of LUAD, and B cells and CD4+ T cells were significant independent risk factors. The TMB and mutations of KRAS, EGFR, STK11, and TP53 were correlated with GNPNAT1. At last, the correlation analysis showed GNPNAT1 correlated with most of the immune signatures we performed.ConclusionOur findings showed that GNPNAT1 was correlated to the prognosis and immune infiltration of LUAD. In particular, the tight relationship between GNPNAT1 and B cell marker genes may be the epicenter of the immune response and one of the key factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of GNPNAT1 in LUAD.

Project description:BackgroundLung cancer is the leading cause of cancer-related death, and adenocarcinoma is the most common type of lung cancer. Although emerging evidence implicates the role of several aldehyde dehydrogenases in cancer progression, the expression and clinical significance of aldehyde dehydrogenase 3B1 in lung adenocarcinoma has never been studied.MaterialsIn our study, the expression of aldehyde dehydrogenase 3B1 in 250 cases of lung adenocarcinoma was detected with immunohistochemistry, and the patients were further divided into subgroups with different aldehyde dehydrogenase 3B1 expression. Using real-time polymerase chain reaction, we investigated the aldehyde dehydrogenase 3B1 messenger RNA in 20 lung adenocarcinoma and paired normal lung tissues. With the χ2 test, we evaluated the clinical significance of aldehyde dehydrogenase 3B1 by analyzing its correlation with the clinicopathological factors. Propensity score matching was performed to balance the baseline of cohort. With univariate and multivariate analyses, we screened the prognostic factors of lung adenocarcinoma and identified the independent prognostic factors before and after the propensity score matching.ResultsAldehyde dehydrogenase 3B1 expression was significantly associated with the sex and age of patients, tumor size, and histological grade. High expression of aldehyde dehydrogenase 3B1 predicted the poor prognosis (P = .003). Moreover, male patients (P = .020), large tumor size (P = .009), advanced T stage (P = .001), positive lymphatic invasion (P < .001), and advanced tumor-node-metastasis stage (P < .001) were all the prognostic factors for unfavorable outcome. Aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma, indicating the poor prognosis. In addition, after balancing the baseline characteristics by propensity score matching, we also demonstrated that aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma (P = .007).ConclusionsAldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma, indicating the unfavorable prognosis. Postoperative detection of aldehyde dehydrogenase 3B1 would help stratify the high-risk patients with lung adenocarcinoma and guide individual treatment.

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Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma.

Publications

Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma.

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